It is clear that myocardial contractile function, and cardiac muscle biochemistry are impaired when ventricular hypertrophy and congestive heart failure result from pressure overload on the heart. This project will explore the biochemistry of cardiac muscle myosin and troponin in an effort to determine if a lesion is present which underlies the mechanical weakness of congestive heart failure (CHF). The mechanism of action of selected pharmacological agents and the possible therapeutic role these agents play in CHF will also be explored. The specific aims of this proposal are: (1) Determine whether digitalis truly prevents damage to the contractile machinery or simply causes a pharmacologic elevation of reduced function. (2) Examine the hypothesis that depression of myosin ATPase activity is associated with the contractile defect and not merely a result of the concomitant hypertrophy. (3) Investigate the possibility that the reduced contractile tension developed by hypertrophied and failing muscle is due, in part, to reduced calcium binding affinity of troponin. (4) Explore the possibility of ameliorating or preventing the contractile defect and myosin ATPase defect by reduction of ventricular preload with consequent fall in wall tension by administration of a venous pooling, vasodilator drug at the initiation of and during pressure overload stress.